1. Field of the Invention
This invention relates generally to systems for diagnosing sleeping disorders, and more particularly, to a system that is useful in effecting rapid diagnosis of, and providing controlled therapy to, patients who suffer from sleep apnea.
2. Description of the Related Art
There is a need in the present state of the art of diagnosing sleeping disorders for automated non-invasive methods that yield objective and reproducible data responsive to the presence of inspiratory flow limitation during sleep. There is a particular need for a system that can perform the necessary acquisition of such data without requiring the use of a pressure-monitoring catheter in the pharynx of the patient.
From the anatomical standpoint, the airways consist of upper and lower airways. Sleep apnea is a common condition that is characterized by obstruction or narrowing of the upper airway. The upper airway segments are the nose, the mouth, and the larynx. The larynx opens to the trachea and branches into two bronchi. Each bronchi enters a lung and terminates in the alveoli. The analysis that is presented herein in support of the present invention focuses on the pharyngeal upper airway. This upper airway consists of the extrthoracic trachea, the larynx, pharynx, and the nose. The principal site for upper airway closure or narrowing during sleep is the pharynx, which is a heterogeneous structure, and it is part of the pharyngeal airway.
The pharyngeal airway is divided into four segments. These segments are the nasopharynx, the velopharynx, the oropharynx, and the hypopharynx. During inspiration, the pharyngeal structure moves forward toward the center of the lumen.
In addition, more than twenty skeletal muscles surround the pharyngeal airway, the muscles being functionally designated as “dilator” muscles and “constrictor” muscles. The pharyngeal muscles receive aphasic activation during inspiration and support a patent pharyngeal lumen through which air flows. Contraction of the pharyngeal muscles can dilate and stiffen the pharyngeal airway, and the constrictor muscles can improve the upper airway patency. The tongue comprises a highly mobile structure that can occlude the pharyngeal airway and the soft palate, which are important in maintaining upper airway patency. It is also known that the tongue is a major muscle comprising protrude and retractor muscles. Either co-activation of the protrude and the retractor muscles, or independent activation of the protrude muscles, can improve upper airway flow mechanics. Co-activation decreases pharyngeal collapsibility but does not dilate the pharyngeal airway. activation of the tongue protrude muscles results in enlargement of the upper airway.
Before describing the art in greater detail, it may be useful to identify some of the acronyms that are widely used:
AcronymDefinitionAHI →Apnea-hypopnea indexANOVA →Analysis of VarianceCHF →Chronic Heart FailureCPAP →Continuous Positive Airway PressurecRUA →Calculated Upper Airway ResistanceDME →Therapeutic Products from a ResellerDTC →Direct to ConsumerEEG →ElectroencephalographyEMG →ElectromyographyEOG →ElectrooculographyFOT →Forced Oscillation ImpedanceIFL →Inspiratory Flow LimitationIHD →Ischemic Heart DiseaseIPS →DeVilbiss Internet ProcessingSoftwareMEMS →Micromachined Electro-mechanicalPressure SensorsmRUA →Measured Upper Airway ResistanceNIFL →Non-Flow LimitedNPV →Negative Predictive ValueNREM →Stage 2 sleep (non-REM?)OSA →Obstructive Sleep ApneaPAP →Positive Airway PressurePAT →Peripheral Arterial TonePPV →Positive Predictive ValuePSG →PolysomnographyREM →Rapid Eye Movement sleepRUA →Upper Airway ResistanceSDB →Sleep-Disordered BreathingSPC →Superior Pharyngeal ConstrictorUARS →Upper Airway Resistance Syndrome
Studies of OSA subjects indicate that activation of the superior pharyngeal constrictor (“SPC”) muscle is similar to the action of pharyngeal dilator muscles during spontaneous and induced apneas. However the effect of each single muscle in regard of sleep obstruction is not yet clear. It has been reported that the mechanical properties of the upper airway is independent of the dilator skeletal muscles that surround it. Also, the prior art is asserted to have determined that pressure is correspondingly equivalent to volume expansion. In other words, although the specific effect of each muscle is not clear in the present state of the art, the ratio of pressure to volume expansion is 1:1, irrespective of whether the dilator muscles are in active or passive conditions.
Inspiratory flow limitation (“IFL”) is the mechanical corollary of snoring and corresponds to a narrowing of the upper airway of a patient. The detection of inspiratory flow limitation will improve the diagnosis of sleep disordered breathing. In the present state of the art, the detection of inspiratory flow limitation typically is achieved by a trained observer who analyzes each breath individually. Such a trained observer will study visually the shape of the time-flow curve that characterizes each breath under consideration. This labor intensive methodology, particularly since it applies a measure of subjectivity to a relatively few breaths, is not adequately precise to achieve an objective and fully reproducible determination of the presence of air flow limitation, and will often result in false diagnoses.
There are available in the art standardized procedures for detecting flow limitation based on analysis of the pressure-flow aspect of the respiration cycle. The known methods, however, are practicable only in sleep research laboratories, and typically are not available in the clinical sleep lab. In the clinical environment, a physician typically will spend about two hours to analyze only about 40 patient breaths. Clearly, the known process is time consuming, functions on a very limited data set, and is likely to produce erroneous results.
Obstructive steep apnea is a condition that is characterized by cessation of breathing during sleep, the air flow being obstructed in the upper airway of the subject. IFL during sleep is defined as decreasing supraglottic pressure without corresponding increase in airway flow rate. This condition generally causes repetitive disturbances during sleep resulting from inadequate flow of air into the lungs of the subject. It is known in the art that resistance to the flow of air is increased during the transition from a state of wakefulness to sleep. A characteristic cross-sectional area can readily be determined in relation to the linear portion of the pressure-flow loop, i.e., corrsponding to a progressive increase in air flow resistance.
There is present in this model a coupling condition that is responsive to the characteristics of the solid structure (i.e., tissue and muscles) of the upper airway and the air flow. The solid structure is characterized by the arrangement of the muscles, the tissue structure, and the viscous flow, which is the air flow. The state of the art is such that there is no indication that muscles affect the compliance of upper airway. The foregoing notwithstanding, the entire solid tissue structure might have a significant effect on obstruction depending upon the viscoelastic properties. However, since such viscoelastic properties of the upper airway have not been thoroughly studied in the relevant literature, it is expected that an analysis based on such properties would have unacceptable uncertainties in its results. Accordingly, greater certainty is achieved if the analysis approaches the problem from the standpoint of air flow in a collapsible tube.
Upper airway obstruction can be caused by several factors. For example, studies have shown that patient with obstructive sleep apnea have an upper airway cross sectional area that is less than that of normal subjects. Therefore, subjects with small upper airway cross sectional area are more likely to have sleep obstruction.
Adipose tissue is the connective tissue in which fat is stored. This tissue surrounds the pharyngeal upper airway, and it has been asserted that this fat might, due to gravity and mass loading that act on the lumen, reduce the upper airway cross sectional area. Other studies, however, assert afinding that the deposit of fact is not related to the pharyngeal narrowing. Instead, the narrowing depends on the thickness of the muscles. Yet another study shows that there are more fat deposits around the collapsible pharyngeal upper airway in patients diagnosed with obstructive sleep apnea, compared to normal subjects. The cross sectional area of patients with Obstructive Sleep Apnea (OSA) is also less than normal during wakefulness. The foregoing notwithstanding, the mechanical effect resulting from fats deposits has not yet been determined.
Mucosal adhesive forces have been considered in the art. The wall of the upper airway has a lining of mucus. It has been hypothesized that surface adhesive forces plays an important role in determining the mechanical properties of the upper airway. During narrowing this mucus lining add more thickness to the surface of the wall, and correspondingly, surface adhesive forces increase the pressure. Surface adhesive forces are considered important in determining the magnitude of the opening pressure required to prevent the mucus from maintaining contact. In animal experiments, it was found that adding topical lubricant to the upper airway reduce the severity It has also been suggested that decreasing the adhesive characteristic of the surface forces will render the upper airway more resistive to collapsing. Thus, it has been hypothesized that the secretion of the mucus could be an important factor during closure of the upper airway, because this will determine the magnitude of the air pressure required to reopen the airway. In sum, however, the physics in support of reduction of the adhesive forces has yet to be explained.
Others in the art have asserted that pressure gradient (i.e., transmural pressure), plays a role in in the collapsibility of the upper airway. Transmural pressure is the pressure difference between intraluminal pressure (pressure inside the lumen), and the extraluminal pressure (atmospheric pressure). During inspiration the pressure in the pharyngeal upper airway is reduced as the cross sectional area is decreased, and the velocity of the air is correspondingly increased. As the pressure in the thorax region increases negatively in relation to atmospheric pressure, the velocity of the air is reduced. The pressure-velocity relationship is consistent with the well-known Bernoulli equation. Thus, a reduction in the transmural pressure will result in a decreased cross-sectional area. The transmural pressure is defined as intraluminal pressure (Pi) minus surrounding tissue pressure (Pt). Cross sectional area can be minimized as the transmural pressure decreases. The prior art has speculated that the reduction or occlusion in the luminal cross-section is a result of negative intraluminal pressure, or positive (Pt). Therefore, as transmural pressure (Ptm) increases, the cross sectional area increases, and vice versa. During narrowing the intraluminal pressure is always negative, and tissue pressure is positive (with respect to atmospheric pressure).
Thoracic caudal traction is caused by inspiratory thoracic activity resulting from an increase in the cross-section of the upper airway. Caudal traction has two mechanisms. The first mechanism is characterized by the stiffening of the upper airway as longitudinal tension is applied to the upper airway. The second mechanism is the dilation of the pharyngeal airway. It has been reported in the art that caudal traction might transmit sub-atmospheric pressure to the tissue that surrounds the upper airway. In this situation the transmutable pressure increases, whereby the difference between intraluminal pressure, and tissue pressure increases radially, (Ptm=Pinterlunimal−Ptissue) and the collapsibility of the upper airway decreases. Others have found an increase in the maximum inspiratory flow upon observing a decrease in the collapsibility of the upper airway with tracheal displacement. Caudal traction has been shown to increase the maximum VI Max inspiratory flow at all levels of tongue displacement. VI Max was noticeably increased for each tongue and caudal displacement interaction. Caudal displacement affects the critical pressure response of the tongue displacement. Thus, under caudal traction there is observed a corresponding decrease in the critical value, while the tongue was displaced.
Upper airway resistance is an important mechanical characteristic for the airflow in the upper airway. Resistance has been described as an indirect measure for upper airway caliber, and has been asserted to be the most significant factor in determining the upper airway caliber, as measured on the linear portion of the pressure-flow curve. However, the determination of resistance is not valid if flow limitation is present because pressure and flow are not associated any more.
It has been reported that the resistance of the upper airway increase more than normal prior to obstruction. Upper airway resistance syndrome is characterized by repetitive episodes of IFL, and decreases in esophageal pressure leading to recurrent arousal. High upper airway resistance can cause tiredness, excessive daytime sleepiness, and a change in blood pressure. Subjects with high resistance work harder at breathing. It also has been reported that a significant increase in expiratory resistance occurs in such subjects just before the initial occluded inspiratory effort of occlusive apnea obstructive sleep apneas.
Resistance is defined as ΔP/ΔF, where ΔP is the pressure gradient, and ΔF is the flow. There is generally an increase of resistance during transition from wakefulness to sleep. The linear resistance at flow=0.2 l/s as an accepted reference standard. However there is not available in the art adequate literature that can relate resistance to the linear portion of the pressure flow relationship. Some researchers in the art have reported that upper airway resistance could be infinite in patients that have severe narrowing or closure. This condition appears mostly with patients having obstructive sleep apnea/hypopnea.
None of the researchers relate the flow to pressure in laminar or turbulent flow to determine the linear resistance. According to known principles of fluid mechanics, linear resistance usually occurs in the laminar region. Usually linear resistance indicates a progressive decrease in the cross-sectional area at the linear portion of pressure flow loop. Resistance and cross-sectional area are related by the known Poiselle equation in the linear region. Therefore it is important to find an objective method to determine resistance.
The literature that comprises the known prior art indicates that there is not available an objective methodology for determining resistance or inspiratory flow limitation.
It is, therefore, an object of this invention to provide a reduction in the time required to diagnose whether a patient suffers from IFL.
It is another object of this invention to provide a methodology that produces an objective diagnosis of sleep apnea.
It is also an object of this invention to provide a method of diagnosing sleep apnea without requiring the use of a pressure-monitoring catheter.
It is a further object of this invention to provide a methodology that produces an objective determination of airway resistance in a patient.
It is additionally an object of this invention to provide a diagnostic methodology that distinguishes between laminar and turbulent flow in the upper airway of a patient.
It is yet a further object of this invention to provide objective characterization of a sleep apnea condition that will be useful in controlling a therapy therefor.